Comparative Study of Bu/Cy/ATG and Flu/Cy/ATG Conditioning Regimens for Unrelated Donor Hematopoietic Stem Cell Transplantation in Severe Aplastic Anemia.

Unrelated donor hematopoietic stem cell transplantation (URD-HSCT) is a curative option for severe aplastic anemia (SAA), but the optimal conditioning regimen remains unclear. This retrospective study compares Busulfan/Cyclophosphamide/Anti-thymocyte globulin (Bu/Cy/ATG) and Fludarabine/Cyclophosphamide/Anti-thymocyte globulin (Flu/Cy/ATG) protocols to identify the best regimen for SAA patients. We retrospectively analyzed the clinical outcomes of 107 SAA patients who underwent URD-HSCT with Flu/Cy/ATG (n = 63) or Bu/Cy/ATG (n = 44) between November 2012 and December 2022. No significant differences were observed in the cumulative incidence of neutrophil/platelet engraftment, graft failure, graft-versus-host disease (GVHD), or CMV viremia. Overall survival (OS) at 7 years was 95.5% (95% CI: 89.5-100) with Bu/Cy/ATG vs. 85.5% (95% CI: 77.1-94.7) with Flu/Cy/ATG, and failure-free survival (FFS) at 7 years was 95.5% (95% CI: 89.5-100) vs. 83.9% (95% CI: 75.2-93.6). Multivariate analysis identified Bu/Cy/ATG protocol as favorable for OS (Hazard ratio, HR 0.122, 95% CI: 0.021-0.715, P = .020) and FFS (HR 0.090, 95% CI: 0.015-0.538, P = .008). Moreover, multivariate analysis confirmed that the Bu/Cy/ATG regimen significantly reduced the risk of EBV viremia (Relative risk, RR 0.175, 95% CI: 0.026-0.717, P = .032) and post-transplant lymphoproliferative disorder (RR 0.031, 95% CI: 0-0.536, P = .012). Subgroup analysis through multivariate modeling further demonstrated that the Bu/Cy/ATG regimen demonstrated superior OS, FFS and EBV infection outcomes in patients older than 30 years. The Bu/Cy/ATG regimen, compared to Flu/Cy/ATG protocol, offers superior outcomes, including improved OS/FFS and reduced EBV infection, suggesting it may be the preferred choice for SAA patients undergoing URD-HSCT, especially for patients older than 30 years. Larger cohorts and prospective trials are needed to validate these findings.